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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:NCOR1-CYP2C9

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NCOR1-CYP2C9
FusionPDB ID: 57831
FusionGDB2.0 ID: 57831
HgeneTgene
Gene symbol

NCOR1

CYP2C9

Gene ID

9611

1559

Gene namenuclear receptor corepressor 1cytochrome P450 family 2 subfamily C member 9
SynonymsN-CoR|N-CoR1|PPP1R109|TRAC1|hN-CoRCPC9|CYP2C|CYP2C10|CYPIIC9|P450IIC9
Cytomap

17p12-p11.2

10q23.33

Type of geneprotein-codingprotein-coding
Descriptionnuclear receptor corepressor 1protein phosphatase 1, regulatory subunit 109thyroid hormone- and retinoic acid receptor-associated corepressor 1cytochrome P450 2C9cytochrome P-450 S-mephenytoin 4-hydroxylasecytochrome P-450MPcytochrome P450 PB-1cytochrome P450, family 2, subfamily C, polypeptide 9flavoprotein-linked monooxygenasemicrosomal monooxygenasexenobiotic monooxygenase
Modification date2020031320200313
UniProtAcc

O75376

Main function of 5'-partner protein: FUNCTION: Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}.

P11712

Main function of 5'-partner protein: FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031). {ECO:0000269|PubMed:11950794, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:15766564, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:25994031, ECO:0000269|PubMed:7574697, ECO:0000269|PubMed:9435160, ECO:0000269|PubMed:9866708}.
Ensembl transtripts involved in fusion geneENST idsENST00000268712, ENST00000395848, 
ENST00000395851, ENST00000583226, 
ENST00000395857, 
ENST00000461906, 
ENST00000260682, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score30 X 30 X 13=117004 X 3 X 3=36
# samples 334
** MAII scorelog2(33/11700*10)=-5.14789869511231
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: NCOR1 [Title/Abstract] AND CYP2C9 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NCOR1 [Title/Abstract] AND CYP2C9 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NCOR1(16021201)-CYP2C9(96701614), # samples:1
Anticipated loss of major functional domain due to fusion event.NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
NCOR1-CYP2C9 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneNCOR1

GO:0046329

negative regulation of JNK cascade

11931768

TgeneCYP2C9

GO:0008210

estrogen metabolic process

12865317

TgeneCYP2C9

GO:0016098

monoterpenoid metabolic process

16401082

TgeneCYP2C9

GO:0017144

drug metabolic process

19219744|19651758

TgeneCYP2C9

GO:0019373

epoxygenase P450 pathway

7574697

TgeneCYP2C9

GO:0019627

urea metabolic process

19029318

TgeneCYP2C9

GO:0032787

monocarboxylic acid metabolic process

19651758

TgeneCYP2C9

GO:0042738

exogenous drug catabolic process

18619574

TgeneCYP2C9

GO:0043603

cellular amide metabolic process

19651758

TgeneCYP2C9

GO:0046456

icosanoid biosynthetic process

15766564

TgeneCYP2C9

GO:0055114

oxidation-reduction process

16401082|19219744

TgeneCYP2C9

GO:0070989

oxidative demethylation

18619574



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:16021201/chr10:96701614)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across NCOR1 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across CYP2C9 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000395851NCOR1chr1716021201-ENST00000260682CYP2C9chr1096701614+376620992034031127
ENST00000395848NCOR1chr1716021201-ENST00000260682CYP2C9chr1096701614+346517984631021018

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000395851ENST00000260682NCOR1chr1716021201-CYP2C9chr1096701614+0.0005899760.99941003
ENST00000395848ENST00000260682NCOR1chr1716021201-CYP2C9chr1096701614+0.0005992250.99940073

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for NCOR1-CYP2C9

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NCOR1chr1716021201CYP2C9chr10967016141798584HNLDNLLQQHKQKLSKVYGPVFTLYF
NCOR1chr1716021201CYP2C9chr10967016142099693HNLDNLLQQHKQKLSKVYGPVFTLYF

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Potential FusionNeoAntigen Information of NCOR1-CYP2C9 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
NCOR1-CYP2C9_16021201_96701614.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:01KQKLSKVY0.99960.54831018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:25KQKLSKVY0.990.53851018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B08:01LLQQHKQKL0.97370.5512514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B08:09LLQQHKQKL0.9410.5932514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:25QQHKQKLSKVY0.99550.5655718
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:04KQKLSKVY0.97730.57261018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B39:12QHKQKLSKV0.85030.6294817
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:135KQKLSKVY0.99960.56211018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:33KQKLSKVY0.99960.54831018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:125KQKLSKVY0.99960.54831018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:27KQKLSKVY0.99960.55941018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:34KQKLSKVY0.99960.54831018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:50KQKLSKVY0.99940.51621018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:12KQKLSKVY0.99830.51311018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B48:02KQKLSKVY0.67840.60431018
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B08:18LLQQHKQKL0.97370.5512514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-A30:01QQHKQKLSK0.94320.5329716
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B08:12LLQQHKQKL0.62570.694514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-C07:04LLQQHKQKL0.51910.8725514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:30LLQQHKQKL0.20240.6477514
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B48:02HKQKLSKVY0.20050.6044918
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B18:06HKQKLSKVY0.04640.5327918
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-A32:01KLSKVYGPVF0.96890.8231222
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B15:20QQHKQKLSKVY0.96770.641718
NCOR1-CYP2C9chr1716021201chr10967016141798HLA-B35:28QQHKQKLSKVY0.96020.6498718

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Potential FusionNeoAntigen Information of NCOR1-CYP2C9 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
NCOR1-CYP2C9_16021201_96701614.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1343LDNLLQQHKQKLSKV217
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1343NLDNLLQQHKQKLSK116
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1354LDNLLQQHKQKLSKV217
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1354NLDNLLQQHKQKLSK116
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1416LDNLLQQHKQKLSKV217
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1416NLDNLLQQHKQKLSK116
NCOR1-CYP2C9chr1716021201chr10967016141798DRB1-1481LDNLLQQHKQKLSKV217

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Fusion breakpoint peptide structures of NCOR1-CYP2C9

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
5475LQQHKQKLSKVYGPNCOR1CYP2C9chr1716021201chr10967016141798

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NCOR1-CYP2C9

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN5475LQQHKQKLSKVYGP-7.32466-7.43806
HLA-B14:023BVN5475LQQHKQKLSKVYGP-5.39793-6.43323
HLA-B52:013W395475LQQHKQKLSKVYGP-6.70926-6.82266
HLA-B52:013W395475LQQHKQKLSKVYGP-5.9249-6.9602
HLA-A11:014UQ25475LQQHKQKLSKVYGP-5.79744-6.83274
HLA-A24:025HGA5475LQQHKQKLSKVYGP-8.07755-8.19095
HLA-A24:025HGA5475LQQHKQKLSKVYGP-6.21161-7.24691
HLA-B27:056PYJ5475LQQHKQKLSKVYGP-5.0741-6.1094
HLA-B27:056PYJ5475LQQHKQKLSKVYGP-4.35973-4.47313
HLA-B44:053DX85475LQQHKQKLSKVYGP-8.39671-8.51011
HLA-B44:053DX85475LQQHKQKLSKVYGP-3.34895-4.38425

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Vaccine Design for the FusionNeoAntigens of NCOR1-CYP2C9

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
NCOR1-CYP2C9chr1716021201chr10967016141018KQKLSKVYAAACAGAAACTCTCAAAGGTCTAT
NCOR1-CYP2C9chr1716021201chr10967016141222KLSKVYGPVFAAACTCTCAAAGGTCTATGGCCCTGTGTTC
NCOR1-CYP2C9chr1716021201chr1096701614514LLQQHKQKLCTCTTACAGCAGCATAAACAGAAACTC
NCOR1-CYP2C9chr1716021201chr1096701614716QQHKQKLSKCAGCAGCATAAACAGAAACTCTCAAAG
NCOR1-CYP2C9chr1716021201chr1096701614718QQHKQKLSKVYCAGCAGCATAAACAGAAACTCTCAAAGGTCTAT
NCOR1-CYP2C9chr1716021201chr1096701614817QHKQKLSKVCAGCATAAACAGAAACTCTCAAAGGTC
NCOR1-CYP2C9chr1716021201chr1096701614918HKQKLSKVYCATAAACAGAAACTCTCAAAGGTCTAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NCOR1-CYP2C9chr1716021201chr1096701614116NLDNLLQQHKQKLSKAATCTTGACAACCTCTTACAGCAGCATAAACAGAAACTCTCAAAG
NCOR1-CYP2C9chr1716021201chr1096701614217LDNLLQQHKQKLSKVCTTGACAACCTCTTACAGCAGCATAAACAGAAACTCTCAAAGGTC

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Information of the samples that have these potential fusion neoantigens of NCOR1-CYP2C9

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
Non-CancerNCOR1-CYP2C9chr1716021201ENST00000395848chr1096701614ENST00000260682203N

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Potential target of CAR-T therapy development for NCOR1-CYP2C9

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to NCOR1-CYP2C9

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to NCOR1-CYP2C9

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource